Use of nitrogen-containing complexing agents for deodorization and antimicrobial treatment of the skin and textile fibre materials

ABSTRACT

The present invention relates to the use of nitrogen-containing complexing agents for deodorization and antimicrobial treatment of the skin and of textile fibre materials.  
     The complexing agents employed according to the invention have the formula  
                 
 
     in which  
     Q 1 , is Carb 1 ; Carb 2, ; or a radical of the formula —(CH 2 ) m     1   —OH  
     Q 2  is hydrogen or Carb 2 ; and  
     Q 3  is Carb 3 ; an amino acid radical; or a radical of the formula (1a)  
                 
 
     where Carb 1 , Carb 2  and Carb 3  independently of one another are the radical of a C 1 -C 8 -mono- or -dicarboxylic acid and  
     m 1  is 1 to 5.  
     The complexing agents according to the invention show a pronounced bacteriostatic action against Corynebacterium xerosis (bacteria which cause body odour) and are therefore suitable as the antimicrobial active substance in body care compositions and antimicrobial fabric finishing of textile materials.

[0001] The present invention relates to the use of nitrogen-containingcomplexing agents for deodorization and antimicrobial treatment of theskin and of textile fibre materials.

[0002] It is known that various nitrogen-containing complexing agents,for example ethylene-diaminetetraacetic acid (EDTA), nitrilotriaceticacid (NTA), β-alaninediacetic acid (EDETA) or ethylenediaminedisuccinicacid (EDDS) are widely employed in domestic detergents because of theircomplexing properties.

[0003] Surprisingly, it has been found that certain nitrogen-containingcomplexing agents also have an antimicrobial action againstGram-positive bacteria and are therefore particularly suitable fordeodorization and antimicrobial treatment of the human skin and oftextile fibre materials.

[0004] The present invention therefore relates to the use ofnitrogen-containing complexing agents for antimicrobial treatment of theskin and of textile fibre materials.

[0005] Compounds which are preferably used according to the invention ascomplexing agents are those of the formula

[0006] in which

[0007] Q₁, is Carb₁; Carb_(2,); or a radical of the formula —(CH₂)_(m) ₁—OH

[0008] Q₂ is hydrogen or Carb₂; and

[0009] Q₃ is Carb₃; an amino acid radical; or a radical of the formula(1a)

[0010] where Carb₁, Carb₂ and Carb₃ independently of one another are theradical of a C₁-C₈-mono- or dicarboxylic acid; and

[0011] m₁ is 1 to 5.

[0012] Compounds which are particularly preferred here are those of theformula (1) in which the amino acid radical Q₃ has the formula

[0013] and especially compounds of the formula (1) in which

[0014] Q₁ is a monocarboxylic acid; or a radical of the formula—(CH₂)_(m) ₁ —OH;

[0015] Q₂ is hydrogen or a monocarboxylic acid; and

[0016] Q₃ is formula (1b); or a monocarboxylic acid.

[0017] Complexing agents which are of particular interest are those ofthe formula (1) in which Carb₂ and Carb₃, independently of one anotherare the radical of the formula

—[(CH₂)]_(n) ₁ —COOH,  (1c)

[0018] in which

[0019] n₁ is 0 to 5.

[0020] Complexing agents which are important in practice have theformula

[0021] or the formula

[0022] Nitrilotriacetic acid (NTA) is furthermore suitable as thecomplexing agent.

[0023] Other examples of complexing agents which can be employedaccording to the invention are aminotrimethylenephosphoric acid (ATMP)of the formula

[0024] serinediacetic acid (SDA) of the formula

[0025] asparaginediacetic acid of the formula

[0026] methylglycinediacetic acid (MGDA) of the formula (7)

[0027] The nitrogen-containing complexing agents employed according tothe invention can be employed not only as the acid but also in the formof the water-soluble salts, preferably as lithium, sodium, potassium,ammonium and ethanolammonium salts.

[0028] Ethylenediaminedisuccinic acid (EDDS) of the formula (2) has twoasymmetric carbon atoms. Various stereoisomeric forms of this compoundare therefore possible. The (S,S) configuration of EDDS has the formula

[0029] An inexpensive chemical synthesis leads to a mixture of the threeforms S,S; R,R; and meso-EDDS. However, separation of thesestereoisomeric compounds requires a high industrial expenditure.Optically pure (S,S)-EDDS can be prepared with the aid of anActinomycetes strain (T. Nishikiori et al., Production by Actinomycetesof (S,S)-N,N′-ethylenediaminedisuccinic acid, an inhibitor ofphospholipase c; J.Antibiotics 37, 426-427 (1984)).

[0030] The purely chemical preparation of the compound of the formula(9) is carried out in a manner known per se, such as is described, forexample, by J. A. Neal, N. Rose in Inorganic Chemistry,7, 2405 (1985).

[0031] Racemic EDDS can be prepared in accordance with U.S. Pat. No.3,158,635.

[0032] The complexing agents according to the invention show apronounced bacteriostatic action, in particular against Gram-positivebacteria of the skin flora, for example Corynebacterium xerosis(bacteria which causes body odour). They are therefore particularlysuitable as the antimicrobial active substance in body carecompositions, for example soaps, shampoos, foot care products and, inparticular, deodorants, as well as an additive in detergents.

[0033] The invention therefore also relates to a body care compositioncomprising at least one nitrogen-containing complexing agent andcarriers or auxiliaries which are tolerated in comsetics.

[0034] The body care composition according to the invention comprises0.01 to 15, preferably 0.5 to 10, % by weight, based on the total weightof the composition, of a nitrogen-containing complexing agent andauxiliaries which are tolerated in cosmetics.

[0035] Depending on the form in which the body care composition ispresent, it also comprises, in addition to the complexing agent, otherconstituents, for example sequestering agents, dyes, perfume oils,thickeners or consolidating agents (consistency regulators),emmollients, UV absorbers, skin protection agents, antioxidants,additives which improve the mechanical properties, such as dicarboxylicacids and/or Al, Zn, Ca, or Mg salts of C₁₄-C₂₂ fatty acids, and, ifappropriate, preservatives.

[0036] Because of their good water-solubility, the complexing agentsaccording to the invention can be incorporated into the correspondingformulations without problems.

[0037] The body care compositions according to the invention can beformulated as a water-in-oil or oil-in-water emulsion, as alcoholic oralcohol containing formulation, as a vesicular dispersion of an ionic ornonionic amphiphilic lipid, as a gel or solid stick or as an aerosolformulation.

[0038] As a water-in-oil or oil-in-water emulsion, the auxiliary whichis tolerated in cosmetics preferably comprises 5 to 50% of an oilyphase, 5 to 20% of an emulsifier and 30 to 90% of water. The oily phasecan comprise any oil suitable for cosmetic formulations, for example oneor more hydrocarbon oils, a wax, a naturally occurring oil, a siliconeoil, a fatty acid ester or a fatty alcohol. Preferred mono- or polyolsare ethanol, isopropanol, propylene glycol, hexylene glycol, glyceroland sorbitol.

[0039] An anitmicrobial soap has, for example, the followingcomposition:

[0040] 0.01 to 5% by weight of the compound of the formula (2)

[0041] 0.3 to 1% by weight of titanium dioxide

[0042] 1 to 10% by weight of stearic acid

[0043] to 100% of soap base, for example the sodium slats of tallowfatty and coconut fatty acid or glycerols.

[0044] A shampoo has, for example, the following composition:

[0045] 0.01 to 5% by weight of the compound of the formula (2),

[0046] 12.0% by weight of sodium laureth-2-sulfate,

[0047] 4.0% by weight of cocamidopropylbetaine,

[0048] 3.0% by weight of NaCl and

[0049] water to 100%.

[0050] A deodorant has, for example, the following composition:

[0051] 0.01 to 5% by weight of the compound of the formula (2),

[0052] 60% by weight of ethanol,

[0053] 0.3% by weight of perfume oil and

[0054] water to 100%.

[0055] The complexing agents according to the invention are furthermoresuitable for the treatment of textile fibre materials. The fibrematerials are non-dyed and dyed or printed fibre materials, for exampleof silk, leather, wool, polyamide or polyurethanes, and in particularall types of cellulosic fibre materials. Such fibre materials are, forexample, naturally occurring cellulosic fibres, such as cotton, linen,jute and hemp, and cellulose and regenerated cellulose. Textile fibrematerials which are preferably suitable are those of cotton.

[0056] The following examples serve to illustrate the invention.

EXAMPLE 1

[0057] Determination of the Antimicrobial Activities of S,S-EDDS,R,R-EDDS, Racemate of EDDS and EDETA, EDTA and NTA

[0058] Test method: An agar diffusion test is carried out with thefollowing modifications:

[0059] Medium: casein-soya flour peptone agar (caso-agar)

[0060] Test organisms: Corynebacterium xerosis ATCC 373

[0061] Corynebacterium xerosis ATCC 7711

[0062] Corynebacterium minutissimum ATCC 23358

[0063] Procedure: 500 ml of caso-agar are innoculated with 3.5 ml of anovernight culture of the bacteria, diluted 1:100, and caso plates (18ml) are covered with a layer of about 5 ml of the bacteria-containingagar. After the plates have cooled, holes of diameter 1 cm are stampedout with a cork borer. Each stamped-out hole is filled with in each case100 μl of a test substance dilution and the plates are incubated at 37°C. for 2 days. Double-distilled water is employed as the solvent for allthe substances. In the case of EDETA GS, the pH is adjusted to 3.3 byaddition of 1 N NaOH. Chemically prepared S,S-EDDS is adjusted to the pHof 5.6 by addition of 1 N NaOH.

[0064] Controls: Double-distilled water

[0065] The test results are listed in Table 1: TABLE 1 Concen-Inhibitory aureola diameter tration Cory. xerosis Cory. xerosisSubstance [ppm] AUG 7711 ATTC 373 EDETA 10000 5/5¹ 1/1¹ S,S-EDDS 1000015/15¹ 10/10¹ (prepared chemically) S,S-EDDS 10000 15/15¹ 10/10¹(prepared by fermentation EDTA 10000 2/2  5/5  R,S-EDDS 10000 n.d.12/13  R,R-EDDS 10000 n.d. 15/15 

[0066] The test results show that both EDETA, EDTA and the EDDS preparedby fermentation and chemically (═R,R; S,S; R,S) show a pronouncedbacteriostatic action against Corynebacterium xerosis.

[0067] Examples of formulations having a bacteriostatic action

EXAMPLE 2

[0068] Preparation of a Washing Powder Laurylammonium sulfate 8.0%Nonionic surfactants 2.9% Soaps 3.5% Sodium tripolyphosphate 43.8% Sodium silicate 7.5% Magnesium silicate 1.9% Carboxymethylcellulose 1.2%EDTA 0.2% Sodium sulfate 21.2%  EDDS 1% Water to 100%

[0069] The formulation is prepared as follows:

[0070] The solid components are mixed and homogenized in a mortar andstirred with deionized water until a uniform pourable and pumpable paste(slurry) is obtained, which is finally spray-dried.

EXAMPLE 3

[0071] Preparation of a Cleansing Tonic Ethanol 20%  Glycerol 5% PEG-40hydrogenated castor oil 1% (hydrogenated ethoxylated castor oil) EDDS  0.5% Perfume ad libidum Water to 100%

[0072] The formulation is prepared as follows:

[0073] EDDS is dissolved in ethanol. Under stirring at room temperaturePEG-40, glycerol and perfume are added. Finally, the water is added.

EXAMPLE 3

[0074] Preparation of a Deodorant Stick Ethanol 20% Glycerol 30%Propylene glycol 20% Ceteareth-25  3% (= ethoxylated cetyl/stearylalcohol) Sodium stearate  7% EDDS 0,5%  Perfume ad libidum Water to 100%

[0075] The formulation is prepared as follows:

[0076] Sodium stearate is melted at 60° C. Propylene glycol,Cetearath-25 and glycerol are added to the melting until a homogeneousclear suspension is obtained. Finally, the suspension is stirred with aEDDS-solution in an alcohol/water mixture at 50° C. and cooled slowly.

EXAMPLE 4

[0077] Preparation of Soluble EDDS Salts and Deodorant Formulations

[0078] S,S-EDDS is obtained by means of microbiological (WO 96/36725) orchemical synthesis (J. A. Neal et al., Inorg.Chem. 7, 2405 (1968)).Racemic EDDS is prepared from maleic anhydride and ethylenediamine (U.S.Pat. No. 3,158,635).

[0079] A 1% suspension of racemic EDDS or S,S-EDDS is prepared inwater/ethanol (about 7:3) with vigorous stirring. An aqueous solution ofNaOH is metered in with an autoamtic titration device until the pH of 7remains constant for 30 minutes. Any slight milky clouding which occursis removed by filtering through paper.

[0080] By addition of a thickener like hydroxy ethyl cellulose a cleardeodorant formulation which is stable at room temperature, comprisesabout 1% of active substance (based on the tetra-acid) and has askin-friendly pH is obtained.

[0081] If NaOH is replaced by KOH, ammonia or ethanolamine, thecorresponding potassium, ammonium and ethanolammonium salts areobtained. Lithium hydroxide, sodium carbonate, sodium bicarbonate orlaurylamine can also be employed as the base.

EXAMPLE 5

[0082] Detection of the Substantial Antimicrobial Activity of R,S-EDDSSalts on the Skin Formulations 1% of R,S-EDDS/sodium salt (Solutions in30% ethanol): 1% of R,S-EDDS/amine salt (for the preparation, cf.Example 4) Medium: Casein-soya flour peptone agar (caso-agar) Testorganism: Corynebacterium xerosis ATCC 373

[0083] Test method:

[0084] Before application of the test solutions, the underarms arewashed with a non-antimicrobial soap twice for 1 minute each time. Atotal of 6 ml of test product is then applied to the washed, dry skin ofthe underarm. Immediately and 2 hours after application of the testproducts, the EDDS on the skin is extracted by means of discs of filterpaper (2 cm diameter) moistened in 0.9% NaCl solution (pH: 8.2). Forthis, the moist filter disc is placed on the treated skin withoutairbubbles for 4 minutes. The filter discs are subsequently dried atroom temperature and then placed on solid agar media with test bacteria.

[0085] To prepare the solid agar media, 500 ml of liquid agar areinnoculated with 3.5 ml of a 12-16-hour culture, diluted 1:100, of thetest bacteria at 47° C. and caso plates (18 ml) are covered with a layerof about 5 ml of the bacteria-containing agar.

[0086] After the filter discs have been placed on top, the agar mediaare incubated for 2 days at 37° C. and the inhibition under the filterdisc or the inhibitory aureolas of the filter discs is/are thendetermined.

[0087] The test results are listed in Table 2: TABLE 2 SubstanceInhibitory aureola dia- meter (mm)/inhibition under the filter disc*Coryneb. xerosis ATCC 373 Placebo 0/0 R,S-EDDS (sodium salt) immed- 5/4iately 2 hours 3/4 after application R,S-EDDS (Amine salt) immed-2,5/4   iately 2 hours 2/4 after application

[0088] Explanation:

[0089] 0=good growth (no inhibition)

[0090] 2=inhibited but clear growth (weak inhibition)

[0091] 4=no growth (potent inhibition)

[0092] The test results show that a pronounced inhibition ofCorynebacterium xerosis is achieved with both test substances.

[0093] The test shows that sufficiently high concentrations of EDDS toachieve inhibition of Corynebacterium xerosis are also still present onthe skin 2 hours after the last application.

What is claimed is:
 1. The use of a nitrogen-containing complexing agentfor antimicrobial treatment of the skin and of textile fibre materials.2. The use according to claim 1, wherein a compound of the formula

in which Q₁, is Carb₁; Carb_(2,); or a radical of the formula —(CH₂)_(m)₁ —OH; Q₂ is hydrogen or Carb₂; and Q₃ is Carb₃; an amino acid radical;or a radical of the formula (1a)

where Carb₁, Carb₂ and Carb₃ independently of one another are theradical of a C₁-C₈-mono- or dicarboxylic acid; and m₁ is 1 to 5, is usedas the complexing agent.
 3. The use as claimed in claim 1 or 2, whereinthe amino acid radical Q₃ has the formula


4. The use according to claim 3, wherein Q₁ is a monocarboxylic acid; ora radical of the formula —(CH₂)_(m) ₁ —OH; Q₂ is hydrogen or amonocarboxylic acid; and Q₃ is formula (ib); or a monocarboxylic acid.5. The use according to claim 1 or 2, wherein Carb₂ and Carb₃,independently of one another are the radical of the formula —[(CH₂)]_(n)₁ —COOH,  (1c) in which n₁ is 0 to
 5. 6. The use according to any one ofclaims 1 to 4, wherein the compound of the formula

is employed as the complexing agent.
 7. The use according to any one ofclaims 1 to 4, wherein the compound of the formula

is employed as the complexing agent.
 8. The use according to claim 1,wherein nitrilotriacetic acid is used as the complexing agent.
 9. Theuse of a complexing agent according to any one of claims 1 to 8, whereinthe complexing agent is also in the form of one of its water-solublesalts.
 10. The use according to claim 9, wherein the complexing agent ispresent in the form of its lithium, sodium, potassium, ammonium orethanolammonium salt.
 11. The use of a complexing agent according to anyone of claims 1 to 10 as an antimicrobial active substance againstGram-positive bacteria.
 12. The use of a complexing agent according toany one of claims 1 to 11 in body care compositions.
 13. A body carecomposition comprising a nitrogen-containing complexing agent accordingto claim
 1. 14. A body care composition according to claim 13 in theform of a soap, a shampoo or a deodorant.
 15. The use of a complexingagent according to any one of claims 1 to 10 in textile fibre materials.